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Brain cell advance brings fresh hope for CJD therapies

Nov 2017: CCBS scientists have generated a stem cell-based model of Creutzfeldt-Jakob disease by infecting stem-cell derived astrocytes with prions.

CCBS scientists have developed a new system to study Creutzfeldt-Jakob disease (CJD) in the laboratory, paving the way for research to find treatments for the fatal brain disorder. The advance marks the first time scientists have been able to infect human cells with the proteins in the laboratory.

The researchers generated brain cells called astrocytes from induced pluripotent stem cells. They successfully infected these cells in a dish with prions isolated from brain samples of CJD patients. The infected astrocytes produced more prions and were able to infect neighbouring healthy cells.

Images: iStock.com and Choi et al 2009, BioMedCentral.

Prion diseases cause brain damage that worsens rapidly over time and are invariably fatal. The most common form of prion disease in people is sporadic CJD, which occurs spontaneously in the population. Around one in a million people in the UK are affected each year.

CJD is similar to Bovine Spongiform Encephalopathy (BSE) in cows and Chronic Wasting Disease in deer. Until now, the only way to study the human form of the disease has been in animals. These studies have yielded valuable information but the relevance of the findings for CJD has been unclear.

The research also demonstrates the potential of human stem-cell derived astrocytes to notably reduce, and in many instances replace, animal studies of human prion disease. The team says this could make a significant contribution to lowering the number of animals used in research in line with the principles of the 3Rs – Reduction, Replacement, Refinement – which are a central tenet of the ethical use of animals in research.

Creutzfeldt-Jakob disease was first reported almost 100 years ago but remains a universally fatal disease. We still have little understanding of what triggers the condition and how it is spread.

Our study reports the first physiologically relevant model for studying human prion diseases in the lab. We hope it will lead to discovery of the key molecular and pathogenic events of prion disease, which could reveal new opportunities for treatments and facilitate drug screening.

Dr James AlibhaiNational CJD Research & Surveillance Unit, Centre for Clinical Brain Sciences

The study is published in the Journal of Experimental Medicine and was funded by the National Centre for the Replacement, Refinement & Reduction of Animals in Research (NC3Rs). The researchers collaborated with experts from the University of California, San Francisco (UCSF) on the project.

Related links

Read the scientific paper: Human stem cell–derived astrocytes replicate human prions in a PRNP genotype–dependent manner. DOI: 10.1084/jem.20161547

Prion disease research at the Centre for Clinical Brain Sciences

National CJD Research and Surveillance Unit